Sclerostin, an osteocyte-secreted protein, negatively regulates osteoblasts and inhibits bone formation (Am. J. Hum. Genet. 2001 March; 68(3):577-89). Likewise, DKK1 plays a key role in regulating bone development and remodeling (J. Orthop. Res. 2011 March; 29(3):414-8). Both of these molecules regulate the Wnt pathway by inhibiting Wnt activity. Inhibition of these Wnt regulators has been shown to change bone density making them attractive targets for therapeutic intervention to treat diseases and disorders associated with bone loss (J Bone Miner Res. 2011 January; 26(1):19-26; Blood Jul. 9, 2009 vol. 114 no. 2; 371-379).
Thus there is a need in the art to generate additional therapeutics that are stable, have desirable half lives, lack immunogenicity and are capable of high efficiency production that further inhibit sclerostin, DKK1 or both.